Storage and dispensing of blood gas quality control reagent from a pressurized container

ABSTRACT

Disclosed is an apparatus for storing blood gas quality control reagent comprising a first variable volume, gas impermeable container for receiving the reagent. The reagent is stored exclusively in the liquid phase therein. A valved exit passageway emanates from the container which container is situated in a second container surrounding the first, a space being present therebetween and a compressed gas situated in the space. Upon opening the valve, the compressed gas decreases the volume of the first container and reagent is expelled through the exit passageway. The present device is uneffected by changes in ambient temperature since the reagent is stored exclusively in the liquid phase. The device is reusable since a portion of the reagent may be expelled without contamination of the remaining contents.

This is a continuation of application Ser. No. 177,211 filed Aug. 11,1980 now abandoned, which is a division of application Ser. No. 003,072filed Jan. 12, 1979. now U.S. Pat. No. 4,266,941.

Background Of The Invention

This invention relates in general to blood gas analyzers, and inparticular, it relates to a device for and a method of assuring that theresults obtained from a blood gas analyzer meet a quality controlstandard.

Blood gas analyzers are becoming increasingly important as analyticaltools in medical laboratories. Blood gas analyzers typically measure thepartial pressure of oxygen and carbon dioxide gases (P₀.sbsb.2 and PCO₂)found in blood samples. These measurements, along with a ph measurementof the blood sample, provide an accurate determination of the body'smetabolism and thus provide a monitor of the patient's cardiopulmonarysystem.

Blood gas analyzers provide the attending physician with importantinformation so long as the results obtained therefrom are accurate.However, the obtaining of accurate results may be extremely difficultwith these devices since the gas content of the blood sample can beaffected by atmospheric pressure and ambient temperature. Accordingly,the particular collection and analytical techniques employed by thelaboratory must be precisely controlled. For example, blood samplesretrieved from the patient must be isolated from the ambient and aconstant temperature must be adequately maintained.

For a discussion of the clinical techniques employed to insure accurateblood gas analysis, see the article entitled "Reliable Blood GasAnalysis", Antonias L. van Kessel, American Society of ClinicalPathologists, Issue No. 20, 1975.

To insure that a blood gas analyzer is operating properly, it is usuallyfrequently calibrated, at least on a daily basis. By calibration ismeant a check and possible adjustment and readjustment of the blood gasanalyzer to insure that the analyzer output accurately reflects theoxygen and carbon dioxide pressures of the sample at the measuring probeof the instrument. For a discussion of the calibration of blood gasanalyzers, see the article entitled "Calibration of Blood Gas Analyzers"by Allen H. Runck, Proceedings of a Workshop on Ph and Blood Gases heldat the National Bureau of Standards, Gaithersburg, Maryland, July 7 and8, 1975, National Bureau of Standards, Special Publication No. 450.

However, even if a blood gas analyzer is properly calibrated, theresults obtained therefrom, may not properly reflect the patient'scondition. For example, if a batch of samples had been exposed to theambient atmosphere, the blood gas analyzer may accurately determine thegas pressure of the sample, but this may not reflect the gas pressure ofthe patient's blood stream. Or, for example, sensor electrodes in theinstrument may not be at the proper, i.e. body, temperature.Accordingly, a need exists, for not only calibrating blood gasanalyzers, but also for subjecting the results of those analyzers to aquality control check. For discussion of the long felt need for qualitycontrol in blood gas analysis, see articles by Sorensen, Malenfant,Gambino and Noonan from the aforementioned Proceedings of a Workshop onph and Blood Gases held at the National Bureau Standards, Gaithersburg,Maryland, July 7 and 8, 1975, National Bureau of Standards, SpecialPublication 450.

Of these articles the Sorensen and Malenfant articles indicate thattonometry is the preferred method of quality control in blood gasanalysis due to its accuracy. However, tonometry is a relatively timeconsuming procedure, and, as pointed in the Noonan article, tedious andcomplicated quality control measures are ineffective since they are notutilized in busy laboratories. Accordingly, Noonan and Gambino recognizethe desirability of what might be referred to as the ampoule or vialmethod of quality control in blood gas analysis.

In the ampoule or vial method of quality control, a sealed glass ampouleor vial is provided containing a reagent having a known quantity of gasdissolved therein. The reagent may, for example, be a bufferedbicarbonate solution or whole blood. In any event, the contents ofdifferent vials are periodically inserted into the blood gas analyzerand the results are recorded. These results are compared against resultsobtained from earlier sampled standard vials. If the results obtainedfrom a number of standard vials are consistently different from oneanother, it may be determined that a source of error has beenintroduced.

One problem which has been associated with the ampoule or vial method ofquality control in blood gas analyzers has been that each ampoule orvial is capable of only a single use, for the reason that each time anampoule or vial is opened, the contents thereof are exposed to theatmosphere and the partial pressure of the oxygen and carbon dioxidedissolved in the reagent contained therein begins to change. Becauseeach ampoule or vial is capable of only a single use, the expense ofpackaging and employing these ampoules or vials is great.

Another problem associated with presently available ampoules is the factthat the reagent stored therein is found in both a liquid and a gasphase. At any particular temperature, the reagent in the ampoule willattain equilibrium between the liquid and gas phases. However, as thetemperature of the vials change, the amount of gas dissolved in thereagent also changes. Therefore, before such vials are utilized, it isnecessary to ensure that the vial is at a standard temperature. Manytimes this precaution is not taken in busy laboratories, thus reducingthe effectiveness of a quality control effort.

It would be desirable to provide a device for and a method ofcalibrating a blood gas analyzer and for subjecting the results obtainedfrom that blood gas analyzer to a quality control test which is bothfaster and more easily utilized than the aforementioned tonometry methodand yet which is more economical than the ampoule method of qualitycontrol.

It would also be desirable to provide a device for and a method ofquality control which would also be useful for calibration of blood gasanalyzers.

Additionally, it would be desirable to provide a device for storing areagent for use in the quality control of a blood gas analyzer which isunaffected by ambient temperature.

These objectives have been achieved in the present invention by theprovision of a device for storing a liquid quality control reagent foruse in a blood gas analyzer which comprises a first container ofvariable volume having a reagent contained therein which is exclusivelyin the liquid phase. An exit passageway is provided emanating from thatcontainer and a valve is situated in the passageway. The first containeris situated in a second container and the space between the containersis filled with a compressed gas. Opening of the aforementioned valveallows for the release of the liquid quality control reagent eitherdirectly into the blood gas analyzer or into a syringe from which thereagent is then transferred into the blood gas analyzer.

Since the reagent is stored entirely in the liquid phase in the firstcontainer, the composition of the liquid reagent is unaffected byambient temperature. Further, since the reagent is expelled by means ofcompressed gas which deforms the first container upon opening the valve,the device of the present invention is reusable in that the contents ofthe container are not exposed to the ambient. Accordingly, a number ofquality control tests may be accomplished with a single filled device.Since the device is reusable, the expense of separately packaged vialsis avoided and the possibility that the reagent concentration might varyfrom vial to vial is eliminated.

Also disclosed herein is a method of storing a liquid quality controlreagent for use in the blood gas analyzer which comprises the steps ofproviding the aforementioned first container for receiving the liquidquality control reagent therein, the container having an input portprojecting therefrom. Subsequently, the first container is overfilledwith the reagent such that the liquid level in the container extendsinto the input port. The container is then sealed at the input port butbelow the liquid level and finally the container is externallypressurized. The employment of this method allows for the storing ofliquid quality control reagent entirely in the liquid phase therebypreventing variation in the reagent parameters with temperature.

The present invention will be more fully understood by reference to theaccompanying drawings in which:

FIG. 1 is a perspective view of a blood gas analyzer into which aquality control reagent is being dispensed from the device of thepresent invention;

FIG. 2 is a partial cross-sectional view of a device for storing a bloodgas quality control reagent according to the present invention;

FIG. 3 is cross-sectional view of a nozzle means for use with the devicefor storing reagent of the present invention; and

FIGS. 4A-E are a plurality of side elevational views, some in partialsection, illustrating a method of storing liquid quality control reagentaccording to the present invention.

Referring first to FIG. 1, a blood gas analyzer is shown generally at10. The blood gas analyzer 10 may comprise as an example the CorningModel 165 which comprises a control panel 12 for selecting a particularmode of operation. For example, the analyzer may make a determination ofP_(O).sbsb.2, P_(CO).sbsb.2 or ph by the proper mode selection at panel12. An input terminal 14 is provided for the receipt from patients ofblood samples which are to be analyzed.

Upon selecting a particular mode of operation, for example adetermination of P_(CO).sbsb.2, a blood sample is introduced from asyringe into input terminal 14 and the partial pressure of the carbondioxide dissolved in that sample is displayed at output panel 16.However, in accordance with the present invention, blood gas qualitycontrol reagent is periodically inserted into the input terminal 14 froma device 16 for storing quality control reagent which will be more fullydescribed in connection with FIG. 2. Alternatively, reagent may beremoved from the device 16 into a syringe (not shown) and inserted intothe input terminal 14 from that syringe.

Referring now to FIG. 2, a device 16 for storing a liquid qualitycontrol reagent is described. Device 16 comprises a first container 18.The container is of variable volume and is gas impermeable. Preferably,the container is formed of a metal such as aluminum having an internalcoating which is non-reactive with standard blood gas quality controlreagents. One exemplary coating of this type would be epoxy. Thecontainer 18 is of a relatively light gauge so as to form a collapsibletube. Situated within the container is a quantity of blood gas qualitycontrol reagent 19. This quality control reagent 19 may be a bufferedbicarbonate solution, for example, such at that disclosed in U.S. Pat.4,001,142 to Turner. Alternatively, the blood gas quality controlreagent could also comprise chemically preserved whole blood. Situatedat one end of the first container 18 is an end cap 20 which is sealed tothe first container by means of a crimp 22. A sealant may be provided atthe crimp 22 to prevent leakage of the reagent. Projecting through theend cap is an exit passageway 24 having a valve 26 or other reusablesealing means situated therein.

The valve 26 is a unidirectional exit valve biased in the closedposition by means of a spring 28.

In the preferred embodiment, the end of the first container 18 oppositepassageway 24 terminates in a neck region 30 having an input port 32therein. The input port is sealed by means of a plug 34 which, like thecontainer 18, is gas impermeable and relatively inert such as a glassmaterial or metal. The plug 34 may be covered with a malleable plasticjacket which acts as a gasket, if desired.

In accordance with an important aspect of the present invention, thequality control reagent 19 found in the first container 18 is storedcompletely in the liquid phase inasmuch as no air space is presentwithin the container. Accordingly, to prevent the first container fromrupturing in the event that it is subjected to elevated or freezingtemperatures, flutes or indentations 36 are provided therein. Theseflutes 36 deform outwardly in the event the reagent 19 expands. Thefirst container 18 is surrounded by and situated within a secondcontainer 38 except at a collar portion 40 at which the first container18, second container 38 and end cap 20 are joined. A space 42 isprovided between the first container 18 and the second container 38 inwhich a compressed gas such as air may be found. The compressed gas ispreferably introduced through an opening in the bottom of the secondcontainer 38 which is closed by a stopper 44. The output end of the exitpassageway 24 is preferably provided with a nozzle 46, one embodiment ofwhich will be more fully described in connection with FIG. 3.

Referring now to FIG. 3, the nozzle 46 includes a sleeve 48 whichsurrounds and mates with the exit passageway 24. The sleeve 46 has acentral passageway 50 therein from which emanate a plurality of radiallyprojecting openings 52. The sleeve terminates in a cylindrical body 54having a conical end 56. Surrounding the cylindrical body 54 and theopenings 52, a means for preventing return flow of expelled liquidcomprising an elastometic tube 58 may be provided. Surrounding thesleeve 48 and the tube 58 is a tapered body 60 which defines an exitchamber 62 between itself and the tube 58 and sleeve 48. The exitchamber 62 communicates with the external environment through an opening64.

Blood gas reagent passing through exit passageway 24 upon opening ofvalve 26 passes through central passageway 50 and then is directedradially through openings 52 causing the radial expansion of the tube58. The fluid then enters the exit chamber 62 from which it passesthrough opening 64 into a syringe (not shown) for ultimate entry intothe input terminal 14. As shown in FIG. 3, the opening 64 is situated ina female type depression 65 for receipt of the tip of a syringe.However, it should be understood that opening 64 could terminate at amale type projection for direct insertion of the reagent to inputterminal 14. The tube 58 is provided such that fluid, once removed fromthe device 16, will not return thereto in order that contamination ofthe remaining blood gas reagent found in the device 16 will be avoided.

In most blood gas analysis equipment, it is desirable that blood gasreagent exiting from the opening 64 not exceed a rate of about 0.5 ccper second. Accordingly, the passageway 24 may be further provided witha means for limiting the outflow of side reagent such as the porous flowrestrictor 66 shown within the central passageway 50 in FIG. 3.

Referring now to FIG. 4A-4E, a method by which the device shown in FIG.2 is filled with the liquid quality control reagent 19 and a method ofstoring the liquid quality control reagent solely in the liquid phasewill be described. As seen in FIG. 4A, the first container 18 havingflutes 36 therein is provided. The container 18 is open at end 68 andalso at the neck region 30.

As seen in FIG. 4B, the end cap 20 having exit passageway 24 with valve26 therein is attached to an upper end 68 of the first container 18. Theend cap 20 and first container 18 are sealed together by means of acrimp 22 as shown in FIG. 2.

As seen in FIG. 4C, the first container 18 is inverted and liquidquality control reagent 19 is inserted into the input port 32 found inthe neck region 30 of the container 18 from a reagent supply sourcethrough line 70. The container is overfilled such that the reagentextends into the input port. As shown in FIG. 4D, the input port is thensealed by means of a plug 34 which projects into the input port 32 atleast as far as the liquid level therein, thus leaving no air spacewithin the container.

Next, as shown in FIG. 4E, the walls of the input port 32 are swagedsuch that they are compressed against plug 34.

Applicant has discovered that it is desirable to employ a plug 34 ratherthan to merely crimp the neck region 30 upon itself, since the provisionof plug 34 prevents rupture of the coating on the interior of thecontainer 18. Rupture of this coating provides localized points at whichcorrosion occurs, thus contaminating the quality control reagent 19.Additionally, applicant has discovered that the use of an inert, gasimpermeable plug, preferably glass, prevents additional contamination ofthe reagent 19.

Finally, the filled container 18 shown in FIG. 4E is inserted into asurrounding second container 38 such as that shown in FIG. 2 and gasunder pressure is provided in the space 42 therebetween.

While the present invention is particularly adapted to the storage ofliquid quality control reagent for use in blood gas analyzers, thoseskilled in the art will realize that the instant device has utility inthe storage of other laboratory reagents which might be affected bycontact with the ambient such as background reagents for use in liquidchromatography. Accordingly, while particular embodiments of the presentinvention have been shown and described, various modifications may bemade without departing from the principles of the invention. Theappended claims are, therefore, intended to cover any such modificationwithin the true spirit and scope of the invention.

What is claimed is:
 1. A device for storing blood gas quality controlreagents comprising:a first container having said blood gas qualitycontrol reagent therein, said container having a variable volume andbeing gas impermeable, said blood gas quality control reagent beingexclusively in the liquid phase, said first container having an inputport projecting from said first container for entry of said reagent; anexit passageway emanating from said first container; a valve situated insaid passageway; a second container surrounding at least a portion ofsaid first container, a space being present therebetween; and acompressed gas situated in said space capable of deforming said firstcontainer upon the opening of said valve whereby said blood gas qualitycontrol reagent is expelled through said passageway.
 2. The device ofclaim 1 wherein said valve is a undirectional exit valve.
 3. The deviceof claim 1 wherein said first container is formed of metal.
 4. Thedevice of claim 1 wherein said first container comprises a collapsibletube.
 5. The device of claim 4 wherein said tube comprises flutes alongthe length thereof.
 6. The device of claim 1 further comprising a meansfor limiting the outflow of said reagent when said valve is completelyopen to a rate of 0.5 cc. per second.
 7. The device of claim 1 furthercomprising a plug for sealing said input port.
 8. The device of claim 7wherein said plug comprises glass.
 9. The device of claim 1 wherein saidblood gas quality control reagent comprises a buffered bicarbonatesolution.
 10. The device of claim 1 wherein said blood gas qualitycontrol reagent comprises whole blood.
 11. the device of claim 1 furthercomprising a nozzle means including a means for preventing a return flowof said expelled reagent into said first container.